Utilization of two protein markers has the potential to replace most testicular biopsies in men with fertility issues. The two germ cell–specific proteins are effective at differentiating men with infertility and identifying subtypes of azoospermia (nonmeasurable levels of sperm in semen), according to a study published Nov. 20 in Science Translational Medicine. Currently a testicular biopsy is a necessary, but imperfect technique to determine if a man has viable sperm that can be utilized in assisted reproduction. But a new test incorporating these two germ-cell protein markers may spare men unnecessary biopsies and surgeries and can provide more accurate assessment of histopathological subtypes of nonobstructiveazoospermia (NOA) and predict the success of testicular sperm extraction (TESE). The two markers (epididymis-expressed ECM1 and testis-expressed TEX101) differentiated obstructive azoospermia (OA) and NOA with high specificities and sensitivities. Using a cutoff level of 2.3 mg/ml OA was distinguished from normal spermatogenesis with 100 percent specificity, while OA was distinguished from NOA with 73 percent specificity and 100 percent sensitivity. TEX101 semen concentrations differentiated the Sertoli cell–only (SCO) syndrome subtypes of NOA using a cutoff of less than 5 ng/ml and hypospermatogenesis (HS) or maturation arrest (MA) subtypes (at 5 to 120 ng/ml in this data set). The authors say that men with biomarker evidence of OA, HS, and MA are recommended for TESE and have high chances of successful sperm retrieval, whereas in men with SCO identified by this test, sperm retrieval is unlikely and TESE could be avoided. “Testing a semen sample can be done in the doctor’s clinic as it’s noninvasive and much easier for the patient than surgery,” co-author Keith Jarvi, head of urology at University of Toronto, says in a statement. “We’re one to two years away from rolling the test out to physicians’ offices around the world, but as a urologist and male fertility specialist I’m awfully glad to know that our test shows such promise and is well on its way.” Commercialization of the test is being led by MaRS Innovation (Toronto), which oversees commercialization for discoveries made at University of Toronto hospitals. The test is currently being transferred to an ELISA format so that it can be quickly validated using a “clinically relevant” technology on several hundred waiting samples. Barry Elkind, project manager in the life science division of MaRS Innovation, says that for the North American market a “major service provider” has the option to license the test and discussions are ongoing in the European market with both a “large service provider” and a kit maker. Interest, Elkind says, has been “high” for what he characterizes as a “strong niche market,” in part because there is a clear economic argument behind the test. Currently, four tests totaling $2,000 are used to definitively determine if infertility is caused by OA or NOA. Even if the test is priced in the “hundreds of dollars” there could be “significant” cost savings for testing performed on the “10s of millions” of men diagnosed worldwide with fertility issues annually. Takeaway: Use of a noninvasive diagnostic test for two germ cell–specific proteins associated with male infertility may eliminate the need for invasive biopsies for diagnosis and to determine a male’s chances of assisted reproductive success.